MRI has proven its efficacy in determining the anatomic extent of bone and soft tissue cancers in numerous published studies. However, it lacks diagnostic specificity and in many cases cannot differentiate benign from malignant processes. Studies of 31P MRS in animals and man suggest that malignant tumors have characteristic 31P NMR spectra, including a large phosphomonoester peak. Such characteristics may permit identification of cancers when they occur within tissues that lack such peaks, such as mesenchymal tissues. We examined the feasibility of combned MRI and 31P MRS in a preliminary trial of 34 patients with bone or soft tissue lesions of the extremities or superficial trunk accessible to simple surface coil localization of MRS, studied prior to biopsy or (Radiology, 173:181, 1989). Analyzable spectra were obtained in 30 patients. We found that only one malignant lesion had a phosphomonoester peak area ratio within two standard derivations of the mean of that a bengin lesions. We concluded that the diagnostic specificity of MRS can be improved by combining 31P MRS with MRI, and that a prospective clinical study to test this concept is feasible. A major limitation in this preliminary study was the need for better localization of spectra to the region of interest in order to increase the fraction of patients eligible for the study and to improve spectral characterization of different lesions. This and other limitations have been overcome by the adoption of techniques such as localization of MRS to multiple regions of interest using chemical shift imaging (CSI) and ISIS volume selection. In the proposed study we will use state of the art 31P MRS techniaues to test the diagnostic potential of 31P MRS in a prospective study of 200 consecutive patients prior to biopsy of bone and soft tissue lesions. In addition, we will determine if the 31P MRS spectral parameters correlate with the clinical and histopathological findings. The results should provide a definitive test of the clinical efficacy of MRS and determine the conditions under which it is fesible. In addition, the results may provide useful information about the in vivo spectral features of different types of tumors that have different biological properties, such as degree of differentiation or probability of recurrence.